1. Field of the Invention
The present invention relates to a process for preparing erythromycin A oxime or a salt thereof useful as intermediates for the synthesis of macrolide antibiotics.
2. Description of the Prior Art
Recently, various chemical modifications of natural macrolide antibiotics have been made to develop synthetic macrolide antibiotics having more excellent feature as medicines. Erythromycin A oxime and the salts thereof are important as intermediates of these synthetic macrolide antibiotics.
There are known processes for preparing erythromycin A oxime by reacting erythromycin A with hydroxylamine hydrochloride using various bases such as, for example, barium carbonate (British Patent No. 1,100,504), pyridine (European Patent No. 109,253A), sodium carbonate (Japanese Patent Kokai No. 62-81,399), imidazole (U.S. Pat. No. 4,672,109) and sodium acetate (Japanese Patent Kokai No. 62-87,599).
Also known is a process by which erythromycin A is reacted with hydroxylamine in dry methanol at room temperature to obtain erythromycin A oxime in a moderate yield (Tetrahedron Letters, p. 157, 1970).
Of the above processes, the processes using hydroxylamine hydrochloride as the base have a problem because hydroxylamine hydrochloride is expensive. In addition, the use of an inorganic bases as the base results in formation of a large amount of the inorganic salt, and therefore, troublesome procedures are required for isolation and purification of erythromycin A oxime from the reaction mixture.
On the other hand, the process using free hydroxylamine provides only less than 20% yield of erythromycin A oxime even after reaction for 35 days, so that it is not practical (See Reference Example described below).